THE RELATIONSHIP OF PLAQUES, TANGLES, AND LEWY‐TYPE ALPHA‐SYNUCLEINOPATHY TO VISUAL HALLUCINATIONS IN PARKINSON’S DISEASE AND ALZHEIMER’S DISEASE

Abstract

Objective: Formed visual hallucinations are a common phenomenon in neurodegenerative disorders such as Parkinson’s Disease (PD), Alzheimer’s disease (AD) and Dementia with Lewy bodies (DLB). While Lewy‐type alpha‐synucleinopathy (LTSis the hallmark neuropathological finding in PD and DLB, amyloid plaques and neurofibrillary tangles are the pathological finding in AD. Previous research has linked complex or formed visual hallucinations (VH) to LTS in neocortical and limbic areas in patients with PD and DLB. As VH also occur in Alzheimer’s disease, and AD pathology often co‐occurs with LTS, we questioned whether this pathology might also be linked to VH. Methods: We performed a semi‐quantitative neuropathological study across brainstem, limbic, and cortical structures in subjects with a documented clinical history of VH and a clinicopathological diagnosis of Parkinson’s disease (PD), Alzheimer’s disease (AD), or dementia with Lewy bodies (DLB). 173 subjects – including 50 with VH and 123 without VH – were selected from the Arizona Study of Aging and Neurodegenerative Disorders. Clinical variables examined included the Mini‐mental State Exam, Hoehn & Yahr stage, and total dopaminergic medication dose. Neuropathological variables examined included total and regional LTS and plaque and tangle densities. Results: A significant relationship was found between the density of LTS and the presence of VH in all diagnostic groups. Plaque and tangle densities also were associated with VH in PD (p=.003 for plaque and p=.004 for tangles), but not in AD, where densities were high regardless of the presence of hallucinations.. Conclusion: Plaques and tangles as well as LTS may contribute to the pathogenesis of VH. Incident VH may be a clinical indicator of underlying pathological events: the development of plaques and tangles in patients with PD, and LTS in patients with AD.